To enable the database analysis and the docking, we develop novel, state of-the-art computational tools which are unique in speed and capabilities. These include a sequence order-independent multiple structure alignment routine that simultaneously compares all structures, and finds in around aminute of CPU on a workstation the optimally conserved structural motif; A rapid method for flexible protein structure comparisons with no predefinition of the hinges (in seconds); Rigid-body and hinge-bendingdocking algorithms which consider entire protein surfaces, and carry out docking in minutes as compared to days by other methods; Develoment ofalgorithms for finding cavities on protein surfaces; Comparisons of databases of drugs, allowing rotations on covalent bonds. Furthermore, we are developing an algorithm for detection of small molecule binding sitethat would bind specific small molecule ligands/drugs.